Mamas on Bedrest: Biological Aspects of Post Partum Depression-Part II

December 17th, 2012

In our last post, we learned that there are specific physical changes that occur in pregnancy that put women at risk for Post Partum Depression (PPD). In most women, these changes self correct in the post partum period. However, for many women, re-regulation does not take place. And in women with susceptible anatomy, these changes put them at increased risk of developing Post Partum Depression. Below, we share information from a recent publication that discusses how the changes that occur as a natural course of pregnancy can contribute to a woman developing PPD.

Changes in Post Partum Depression


Low levels of estrogen and progesterone have been shown to be associated with PPD, but cannot be said to be causative as there have been studies in which participants had elevated levels of estrogen and/or progesterone and had PPD. However, estrogen therapy-in relatively large doses-does seem to improve PPD.

PPD being linked to suppression of the HPA has been substantiated in several studies. Women with PPD have markedly suppressed HPA and their HPA’s don’t return to their baseline regulation as does those of women not subject to PPD.

Oxytocin, the milk let down hormone, seems to have a positive mood altering effect. However, when women have difficulty with breastfeeding or stop breastfeeding, they often are at increased risk for developing PPD. This point remains controversial as some women, it seems, stop breastfeeding because they are depressed. Oxytocin does seem to have a suppressive effect on the HPA

As previously stated, Serotonin seems to play a prominent role in PPD.  Low levels of serotonin are indicative of depression and medications that increase serotonin levels (SSRI’s) successfully treat PPD. Other neurochemicals and neurogenetic predispositions that influence the serotonin levels, typically suppression of serotonin production and release, further put women with these chemical anomalies or genetic predispositions are at increased risk for developing PPD.

Seasonal/circadian Changes

Newer research in PPD shows that there are seasonal effects, i.e. PPD may in fact be more prevalent in the fall and winter months, as SAD.

High morning levels of Melatonin are associated with PPD. Melatonin is made from serotonin but when secreted in the morning, when one is to awaken instead of at night when one is trying to sleep, increases sleep deprivation and sleep deprivation is a hallmark of PPD. Unfortunately, sleep disturbances are also a hallmark of the early post partum period, so it is often hard to discern if the Melatonin levels are abnormal due to depression or due to post partum sleep disturbances. For now, studies suggest that high am blood levels of Melatonin are present in women with PPD. More work in this area is forthcoming.

Immunologic Changes

Inflammation plays a roll in PPD. As previously stated, cortisol levels are increased during pregnancy (due to the maternal/fetal interaction) and the feedback loop telling the adrenals that there is enough cortisol is shut down. Without the adrenals functioning, at delivery, cortisol levels drop and the inflammatory response is left unchecked. Increases in inflammation is the result of a prolonged inflammatory response which has been shown to be a way for PPD to develop.

Thyroid Disease

Abnormal thyroid function appears to be associated with increased psychiatric symptoms, with hyperthyroidism being related to anxiety, mania, restlessness, depression and cognitive deficits and hypothyroidism is associated with memory deficits, lack of concentration, psychomotor slowing and depression.

Pregnancy in and of itself challenges normal thyroid function, often resulting in the presence of thyroid antibodies. During pregnancy TSH levels fluctuate depending on the stage of pregnancy while levels of T3 and T4 remain relatively stable within normal limits. In the early post partum, TSH levels are decreased. Of note, thyroid hormone replacement in the post partum doesn’t seem to prevent or reduce PPD symptoms in the presence of thyroid antibodies.  Currently, these authors are only able to report that

Women with maternity blues have higher TSH levels  and women with higher, albeit still normal, TSH levels (measured 4 weeks after delivery) tended to have higher depression scores at 4-weeks postpartum.  In addition, the authors reported a positive association between subclinical hypothyroidism at delivery and the development of self-reported depressive symptoms at 6 months post partum.

Given this information, the best thing to do in a woman with PPD symptoms would be to test for thyroid function and treat accordingly.

Other Potential Factors in PPD

Vitamin D. It seems that Vitamin D is being found to affect everything from our moods to our weights and everything in between, so it’s no surprise that it has an effect on PPD. What is surprising is that fact that recent studies have reported associations between vitamin D deficiency, inflammatory response and mood disorders.

As it relates to PPD, the authors note that Vitamin D levels have been found in postpartum women compared with pregnant women, but there is  so far only one study in the literature, examining serum 25(OH)D levels postpartum in relation to Edinburgh Postpartum Depression Scale scores. That particular study shows a significant association over time between low 25(OH)D levels and high depression scores postpartum. Thus far, only one randomized clinical trial has evaluated treatment with high doses of vitamin D in depressed subjects with promising results.


Although Leptin is most closely associated with satiety and obesity research, recent research has linked leptin with depression and reproductive function in women. Leptin is reported to rise during pregnancy, fall after delivery and subsequently increase during the first 6-months postpartum. A study by these authors showed that higher leptin levels at delivery provided protection against depressive symptoms at 5-days, 6-weeks and 6-months post partum. Several theories are suggested for the protection, but to date, there is no definitive explanation.

This is a very interesting and important article. This level of indepth research is much needed if we are ever to be able to effectively treat (and perhaps even prevent) PPD. As these authors showed, there are multiple mechanisms potentially responsible for post partum depression. It is no longer enough to “poo poo” it away as mood, fatigue, being a new mommy or to ignore the signs and symptoms all together. Each and every pregnant and post partum patient should be routinely asked if they have any signs or symptoms of mood changes, and prompt and aggressive evaluation and treatment should be undertaken to ensure that mamas in need, receive the help and care necessary.


Alkistis Skalkidou, Charlotte Hellgren, Erika Comasco, Sara Sylvén & Inger Sundström Poromaa. Biological aspects of postpartum depression. Women’s Health, November 2012, Vol. 8, No. 6, Pages 659-671.  DOI 10.2217/whe.12.55 (doi:10.2217/whe.12.55)

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